Most research strategies for cartilage tissue engineering use extended culture with complex media loaded with costly GFs (growth factors) to drive tissue assembly and yet they result in the production of cartilage with inferior mechanical and structural properties compared with the natural tissue. Recent evidence suggests that GAGs (glycosaminoglycans) incorporated into tissue engineering scaffolds can sequester and/or activate GFs and thereby more effectively mimic the natural ECM (extracellular matrix). Such approaches may have potential for the improvement of cartilage engineering. However, natural GAGs are structurally complex and heterogeneous, making structure–function relationships hard to determine and clinical translation difficult. Importantly, subfractions of GAGs with specific chain lengths and sulfation patterns have been shown to activate key signalling processes during stem cell differentiation. In addition, recently, GAGs have been bound to synthetic biomaterials, such as electrospun scaffolds and hydrogels, in biologically active conformations, and methods to purify and select affinity-matched GAGs for specific GFs have also been developed. The identification and use of specific GAG moieties to promote chondrogenesis is therefore an exciting new avenue of research. Combining these with synthetic biomaterials may allow a more effective mimicry of the natural ECM, reduction in the need for expensive GFs, and perhaps the deposition of an articular cartilage-like matrix in a clinically relevant manner.

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